Bioengineering the ovary to preserve and reestablish female fertility

Abstract

Different bioengineering strategies can be presently adopted and have been shown to have great potential in the treatment of female infertility and ovarian dysfunction deriving from chemotherapy, congenital malformations, massive adhesions as well as aging and lifestyle. One option is transplantation of fresh or cryopreserved organs/fragments into the patient. A further possibility uses tissue engineering approaches that involve a combination of cells, biomaterials and factors that stimulate local ability to regenerate/ repair the reproductive organ. Organ transplant has shown promising results in large animal models. However, the source of the organ needs to be identified and the immunogenic effects of allografts remain still to be solved before the technology may enter the clinical practice. Decellularization/ repopulation of ovary with autologous cells or follicles could represent an interesting, still very experimental alternative. Here we summarize the recent advancements in the bioengineering strategies applied to the ovary, we present the principles for these systems and discuss the advantages of these emerging opportunities to preserve or improve female fertility.

Whole-ovary decellularization generates an effective 3D bioscaffold for ovarian bioengineering

“…Ovary dysfunction and premature ovarian failure (POF) represent the maiARG001784sn causes of infertility, with an alarming incidence of one out of 1000 women, under the age of 30, rising to 1.0-1.5% in women younger than 40 years [1,2]. Patients affected are not able to undergo physiological cycles and/or release oocytes, nor they produce normal levels of hormones [3]. Infertility is currently considered a multiple medical and psychosocial challenge, since it is accompanied by severe menopause symptoms, such as osteoporosis, cardiovascular disease, autoimmune disorders, and depression [4].…”

Ovarian Decellularized Bioscaffolds Provide an Optimal Microenvironment for Cell Growth and Differentiation In Vitro

“…Adult dermal fibroblasts were isolated from fresh skin biopsies obtained from 5 gilts. Tissues were cut into small fragments of~2mm 3 and transferred into 35 mm 2 Petri dishes (Sarstedt, Milan, Italy) previously coated with 0.1% gelatin (Sigma, Milan, Italy). Droplets of DMEM supplemented with 20% FBS, 2 mM glutamine (Sigma, Milan, Italy), and 2% antibiotic/antimycotic solution (Sigma, Milan, Italy) were added onto each fragment.…”

“…Premature ovarian failure (POF) is a common endocrine disease that leads to early menopause and infertility. It has an incidence of 0.1% in women under 20 years of age and increases to 1.0-1.5% in subjects younger than 40 years [1][2][3]. Radiotherapy, chemotherapy, viral infections, environmental factors, metabolic and autoimmune disorders, and genetic alterations represent some of the potential causes identified so far.…”

Co‐culture with peritoneum mesothelial stem cells supports the in vitro growth of mouse ovarian follicles

“…Chemo-and radiation therapies lead to early menopause, premature ovarian insufficiency (POI), and/or infertility in women. 1,2 One solution to this problem is the transplantation of fresh or frozen ovaries and ovarian tissues, but the risks of recurrence of malignancy in the cells and allogenic rejection of transplants have led to interest in the development of alternate techniques such as in vitro culture of isolated ovarian follicles. [2][3][4][5] Current follicular culture systems are inefficient due to inconsistent development of both somatic and germinal components of the ovarian follicles.…”

“…1,2 One solution to this problem is the transplantation of fresh or frozen ovaries and ovarian tissues, but the risks of recurrence of malignancy in the cells and allogenic rejection of transplants have led to interest in the development of alternate techniques such as in vitro culture of isolated ovarian follicles. [2][3][4][5] Current follicular culture systems are inefficient due to inconsistent development of both somatic and germinal components of the ovarian follicles. 6 Moreover, in vitro cultured follicles have much smaller diameters and are poorer in quality than in vivo follicles.…”